The major goals of these studies are to elucidate the individual roles of COX-1 and COX-2 in normal physiology and in various pathological states using the COX deficient mice. Included in these studies are the roles of the COX isoforms in gastric ulceration, lung inflammation and vascular development. Our early studies in COX deficient mice was to investigate gastric ulceration, inflammatory responses and kidney development. More recent interest in the laboratory has been to study the effects of COX deficiency on lung inflammation and mucus production. Additionally, effort within the laboratory has focused on using COX-1 and COX-2 deficient ES cells to study the roles of the COXs in endothelial cell development. Studies suggest that the deficiency of COX-1 or COX-2 do not inhibit ES cell differentiation into endothelial cells. Studies with COX-1 and COX-2 selective inhibitors have been used and the data obtained suggest that the COX-2 inhibitor inhibits epithelial cell development by a COX dependent mechanism.